Nailpolish: Reference-free UMI deduplication and consensus read generation

Long-read sequencing captures full-length transcripts but suffers elevated error rates, and PCR duplicates can distort quantification unless accounted for with UMIs. We present Nailpolish, a fast reference-free tool that error-corrects and deduplicates UMI-tagged long reads by generating consensus sequences via partial order alignment, while separating false duplicates arising from UMI collisions. Across eleven Oxford Nanopore Technologies and Pacific Biosciences datasets spanning bulk, single-cell, spatial, and targeted protocols, Nailpolish reduced per-read error rates and outperformed existing deduplication tools.